Department of Bioengineering; University of Pittsburgh; Pittsburgh, PA USA; McGowan Institute for Regenerative Medicine; University of Pittsburgh; Pittsburgh, PA USA.
Organogenesis. 2013 Jul-Sep;9(3):149-60. doi: 10.4161/org.25394. Epub 2013 Jun 25.
The current prevalence and severity of heart defects requiring functional replacement of cardiac tissue pose a serious clinical challenge. Biologic scaffolds are an attractive tissue engineering approach to cardiac repair because they avoid sensitization associated with homograft materials and theoretically possess the potential for growth in similar patterns as surrounding native tissue. Both urinary bladder matrix (UBM) and cardiac ECM (C-ECM) have been previously investigated as scaffolds for cardiac repair with modest success, but have not been compared directly. In other tissue locations, bone marrow derived cells have been shown to play a role in the remodeling process, but this has not been investigated for UBM in the cardiac location, and has never been studied for C-ECM. The objectives of the present study were to compare the effectiveness of an organ-specific C-ECM patch with a commonly used ECM scaffold for myocardial tissue repair of the right ventricle outflow tract (RVOT), and to examine the role of bone marrow derived cells in the remodeling response. A chimeric rat model in which all bone marrow cells express green fluorescent protein (GFP) was generated and used to show the ability of ECM scaffolds derived from the heart and bladder to support cardiac function and cellular growth in the RVOT. The results from this study suggest that urinary bladder matrix may provide a more appropriate substrate for myocardial repair than cardiac derived matrices, as shown by differences in the remodeling responses following implantation, as well as the presence of site appropriate cells and the formation of immature, myocardial tissue.
当前,需要功能性心脏组织替代的心脏缺陷的流行率和严重程度对临床构成了严重挑战。生物支架是一种有吸引力的组织工程方法,可用于心脏修复,因为它们避免了同种异体材料相关的致敏性,并且从理论上讲具有与周围天然组织相似的生长潜力。尿路上皮基质(UBM)和心脏细胞外基质(C-ECM)都曾被作为心脏修复的支架进行过研究,取得了一定的成功,但尚未直接进行比较。在其他组织部位,骨髓来源的细胞已被证明在重塑过程中发挥作用,但尚未在心脏部位的 UBM 中进行研究,也从未在 C-ECM 中进行过研究。本研究的目的是比较特定器官的 C-ECM 补片与常用的 ECM 支架在修复右心室流出道(RVOT)心肌组织方面的效果,并研究骨髓来源细胞在重塑反应中的作用。生成了一种嵌合大鼠模型,其中所有骨髓细胞均表达绿色荧光蛋白(GFP),并用于显示源自心脏和膀胱的 ECM 支架在 RVOT 中支持心脏功能和细胞生长的能力。这项研究的结果表明,与源自心脏的基质相比,尿路上皮基质可能为心肌修复提供了更合适的基质,这表现在植入后的重塑反应、适当部位的细胞存在以及不成熟的心肌组织形成等方面的差异。